Objective: Glucocorticoids were found to inhibit adiponectin gene expression and secretion both in vitro and in animal models. We evaluated first the acute effect of i.v. glucocorticoids on adiponectin in normal subjects and secondly plasma adiponectin levels in a series of patients with Cushing's syndrome compared with controls. Design and methods: Hydrocortisone (25 mg) was administered i.v. to five healthy volunteers, with blood samples taken at 215, 0, 30, 60, 120 and 180 min. Twenty-one patients with Cushing's syndrome were divided in two groups: one with 11 obese and the other with 10 non-obese Cushing's patients. Each group was compared with controls that were matched for sex, age, body mass index, waist circumference, glucose, insulin, lipid levels and blood pressure. Results: In normal subjects, hydrocortisone produced a decrease in adiponectin at 30 and 60 min, compared with placebo (P , 0.05). Adiponectin was lower in non-obese Cushing's patients than in non-obese controls (P , 0.004). In contrast, there was no difference in adiponectin levels in obese Cushing's patients and in obese controls. Adiponectin was inversely correlated (P , 0.05) with homeostasis model assessment index in both obese and non-obese Cushing's patients; in nonobese Cushing's patients only, adiponectin was inversely correlated with urinary cortisol (P , 0.05). Conclusions: Glucocorticoids inhibit adiponectin in man, as shown by both exogenous administration to healthy subjects and endogenous cortisol hyperproduction. Similar levels of adiponectin in obese Cushing's patients and their obese controls indicate that obesity per se may act as a predominant factor in masking the relationship between adiponectin and cortisol.

The bradykinin B2 receptor (B2R) gene is a candidate in the pathogenesis of insulin resistance, which often clusters with other abnormalities in metabolic syndrome. We investigated the distribution of the C-58T B2R gene polymorphism within a population of overweight/obese patients (BMI > or = 25 kg/m2) potentially characterised by different levels of insulin resistance. Patients with type 2 diabetes, dyslipidemia and hypertension were excluded in order to distinguish the effect of obesity on insulin sensitivity from that of confounding factors. Ninety-two unrelated adults (41 men and 51 women, aged 33.7 +/- 11.6 years) were recruited by random sampling from a general population evaluated for cardiovascular risk stratification. Measurements included BMI, waist circumference, body composition, blood pressure, serum leptin, and lipid profile. Insulin sensitivity was calculated according to the homeostasis model assessment (HOMA) method. C-58T genotypes--CC (n = 20), CT (n = 47) and TT (n = 25)--were determined by restriction fragment-length polymorphism PCR. Patients subdivided on the basis of C-58T polymorphism, showed no difference in any of the parameters examined, including HOMA index values, after adjustment for age, sex, BMI and waist circumference. The results indicate that the C-58T B2R gene polymorphism is not associated with different levels of insulin resistance within a population of obese patients.